中国临床药理学与治疗学2024，Vol.29Issue(1)：52-60,9.DOI:10.12092/j.issn.1009-2501.2024.01.005
头孢吡肟/阿维巴坦M-H肉汤中浓度测定方法学建立及在体外动态PK/PD模型中的应用
Development and validation of a method for quantitation of ce-fepime/avibactam in M-H broth:application to antibacterial activity using in vitro PK/PD Model
摘要
Abstract
AIM:To establish a method for quanti-tation of cefepime and avibactam in M-H broth,and applicated in the in vitro dynamic PK/PD mod-el.METHODS:The cefepime was also determined using the high-performance liquid chromatography method(HPLC),the avibactam was also determined using the liquid chromatography-mass spectrome-try(LC-MS/MS),an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae(CRKP).RESULTS:The linear ranges of cefepime and avibactam were good at(0.5-20)and(0.1-25)μg/mL(r=0.999),and the low-er limit concentrations were 0.5 and 0.1 μg/mL.The extraction recoveries of cefepime and avibac-tam in M-H broth were 88.0％-101.7％and 90.9％-95.2％,the relative standard deviation of intra-day precision and inter-day precision were less than 5.2％.The concentration-time curves were well sim-ulated by the PK/PD model.All observed concentra-tions in each experiment were in the range of 20％of the targeted values.For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL,the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mLat the cefepime/avibactam 2.5 g q8 h administration after 24 h.CONCLUSION:The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability.For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.关键词
头孢吡肟/阿维巴坦/HPLC/LC-MS/MS/体外动态PK/PD模型Key words
cefepime/avibactam/HPLC/LC-MS/MS/in vitro dynamic PK/PD model分类
药学引用本文复制引用
颜冰倩,郭思维,李尤,田淼梅,徐兵,蒋蓉,李昕..头孢吡肟/阿维巴坦M-H肉汤中浓度测定方法学建立及在体外动态PK/PD模型中的应用[J].中国临床药理学与治疗学,2024,29(1):52-60,9.基金项目
抗耐药微生物药物湖南省重点实验室项目(2023TP1013) （2023TP1013）
湖南省临床医疗技术创新引导项目(2021SK53002) （2021SK53002）
